The distribution of antibiotic use and its association with antibiotic resistance
Abstract
Antibiotic use is a primary driver of antibiotic resistance. However, antibiotic use can be distributed in different ways in a population, and the association between the distribution of use and antibiotic resistance has not been explored. Here we tested the hypothesis that repeated use of antibiotics has a stronger association with population-wide antibiotic resistance than broadly-distributed, low-intensity use. First, we characterized the distribution of outpatient antibiotic use across US states, finding that antibiotic use is uneven and that repeated use of antibiotics makes up a minority of antibiotic use. Second, we compared antibiotic use with resistance for 72 pathogen-antibiotic combinations across states. Finally, having partitioned total use into extensive and intensive margins, we found that intense use had a weaker association with resistance than extensive use. If the use-resistance relationship is causal, these results suggest that reducing total use and selection intensity will require reducing broadly-distributed, low-intensity use.
Data availability
State-level, aggregate antibiotic use and resistance data used in the main analyses are in Figure 3 - Source data 1 and 2. We do not own and cannot publish disaggregated MarketScan or Medicare data. MarketScan data are available by commercial license from Truven Health (marketscan.truvenhealth.com). Medicare data are available from ResDAC (www.resdac.org). ResDAC requires an application ensuring that requesting researchers comply with Common Rule, HIPAA, and CMS security and privacy requirements. Disaggregated ResistanceOpen data are restricted due to hospitals' privacy concerns. ResistanceOpen data are available by request from HealthMap (www.resistanceopen.org).
Article and author information
Author details
Funding
National Institute of General Medical Sciences (U54GM088558)
- Scott W Olesen
- Marc Lipsitch
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Neil M Ferguson, Imperial College London, United Kingdom
Publication history
- Received: June 26, 2018
- Accepted: December 8, 2018
- Accepted Manuscript published: December 18, 2018 (version 1)
- Version of Record published: December 27, 2018 (version 2)
Copyright
© 2018, Olesen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
We are writing to reply to the comment by Pouwels et al., 2019 about our recent study (Olesen et al., 2018) on antibiotic use and antibiotic resistance.
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- Epidemiology and Global Health
Background:
Whether natural selection may have attributed to the observed blood group frequency differences between populations remains debatable. The ABO system has been associated with several diseases and recently also with susceptibility to COVID-19 infection. Associative studies of the RhD system and diseases are sparser. A large disease-wide risk analysis may further elucidate the relationship between the ABO/RhD blood groups and disease incidence.
Methods:
We performed a systematic log-linear quasi-Poisson regression analysis of the ABO/RhD blood groups across 1,312 phecode diagnoses. Unlike prior studies, we determined the incidence rate ratio for each individual ABO blood group relative to all other ABO blood groups as opposed to using blood group O as the reference. Moreover, we used up to 41 years of nationwide Danish follow-up data, and a disease categorization scheme specifically developed for diagnosis-wide analysis. Further, we determined associations between the ABO/RhD blood groups and the age at the first diagnosis. Estimates were adjusted for multiple testing.
Results:
The retrospective cohort included 482,914 Danish patients (60.4% females). The incidence rate ratios (IRRs) of 101 phecodes were found statistically significant between the ABO blood groups, while the IRRs of 28 phecodes were found statistically significant for the RhD blood group. The associations included cancers and musculoskeletal-, genitourinary-, endocrinal-, infectious-, cardiovascular-, and gastrointestinal diseases.
Conclusions:
We found associations of disease-wide susceptibility differences between the blood groups of the ABO and RhD systems, including cancer of the tongue, monocytic leukemia, cervical cancer, osteoarthrosis, asthma, and HIV- and hepatitis B infection. We found marginal evidence of associations between the blood groups and the age at first diagnosis.
Funding:
Novo Nordisk Foundation and the Innovation Fund Denmark